Characterisation of the immune-related transcriptome in resected biliary tract cancers

被引:51
作者
Ghidini, Michele [1 ,2 ,3 ]
Cascione, Luciano [4 ]
Carotenuto, Pietro [1 ]
Lampis, Andrea [1 ]
Trevisani, Francesco [1 ,5 ]
Previdi, Maria Chiara [1 ]
Hahne, Jens C. [1 ]
Said-Huntingford, Ian [1 ]
Raj, Maya [1 ]
Zerbi, Alessandro [2 ,7 ]
Mescoli, Claudia [6 ]
Cillo, Umberto [6 ]
Rugge, Massimo [6 ]
Roncalli, Massimo [7 ]
Torzilli, Guido [2 ,7 ]
Rimassa, Lorenza [2 ]
Santoro, Armando [2 ,7 ]
Valeri, Nicola [1 ,8 ,9 ]
Fassan, Matteo [6 ]
Braconi, Chiara [1 ,8 ,9 ]
机构
[1] Inst Canc Res, 15 Cotswold Rd,Haddow Lab Room 7N1, Sutton SM2 5NG, Surrey, England
[2] Humanitas Clin & Res Ctr, Humanitas Canc Ctr, Via Manzoni 113, I-20089 Milan, Italy
[3] ASST Hosp Cremona, Viale Concordia 1, I-26100 Cremona, Italy
[4] Inst Oncol Res, Via Vela 6, CH-6500 Bellinzona, Switzerland
[5] Ist Sci San Raffaele, Via Olgettina, I-20132 Milan, Italy
[6] Univ Padua, Via Gabelli 61, I-35100 Padua, Italy
[7] Humanitas Univ, Via Manzoni 113, I-20089 Milan, Italy
[8] Royal Marsden NHS Fdn Trust, London, England
[9] Royal Marsden NHS Fdn Trust, Downs Rd, Sutton SM2 5PT, Surrey, England
关键词
Cholangiocarcinoma; CTLA4; Treg; Adjuvant; CD80; HUMAN-MALIGNANT CHOLANGIOCYTES; INTRAHEPATIC CHOLANGIOCARCINOMA; BREAST-CANCER; PHASE-II; EXPRESSION; GEMCITABINE; TUMORS; CELLS; INTERLEUKIN-6; CHEMOTHERAPY;
D O I
10.1016/j.ejca.2017.09.005
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. In these studies, nCounter PanCancer Immune Profiling Panel was used to assess the expression of 770 immune-related transcripts in the tumour tissues (TTs) and matched adjacent tissues (ATs) of resected BTCs. Cox regression analysis and Kaplane-Meier methods were used to correlate findings with relapse-free survival (RFS). The first analysis in the TT and AT of an exploratory set (n = 22) showed deregulation of 39 transcripts associated with T-cell activation. Risk of recurrence was associated with a greater number of genes deregulated in AT in comparison to TT. Analysis in the whole set (n = 53) showed a correlation between AT cytotoxic T-lymphocyte antigen-4 (CTLA4) expression and RFS, which maintained statistical significance at multivariate analysis. CTLA4 expression correlated with forkhead box P3 (FOXP3) expression, suggesting enrichment in T regulatory cells. CTLA4 is known to act by binding to the cluster of differentiation 80 (CD80). No association was seen between AT CD80 expression and RFS. However, CD80 expression differentiated prognosis in patients who received adjuvant chemotherapy. We showed that the immunomodulatory transcriptome is deregulated in resected BTCs. Our study includes a small number of patients and does not enable to draw definitive conclusions; however, it provides useful insights into potential transcripts that may deserve further investigation in larger cohorts of patients. (C) 2017 The Author(s). Published by Elsevier Ltd.
引用
收藏
页码:158 / 165
页数:8
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